FROM THE JULY-AUGUST 2011 ISSUE

The Brain: A Body Fit for a Freaky-Big Brain

Human biology reorganized itself to cope with the punishing burden of our
oversize thinking parts. That shift completely reshaped who we are.
By Carl Zimmer | Tuesday, July 26, 2011

Aiello and Wheeler noted that this dramatic increase in brain size would seem to have required a dramatic
increase in metabolismthe same way that adding an air-conditioning system to a house would increase the
electricity bill. Yet humans burn the same number of calories, scaled to size, as other primates. Somehow,
Aiello and Wheeler argued, our ancestors found a way to balance their energy budget. As they expanded their
brains, perhaps they slimmed down other organs.
The scientists compared the sizes of organs in humans and other primates. Relatively speaking, our liver is
about the same size as a baboons. Our heart is on par with a gorillas. But our guts have shriveled. They
weigh only 60 percent of what youd expect in a primate of our size. Intestinal cells also need a lot of energy,
because they are highly innervated. Losing such a big portion of their guts could have allowed our ancestors
to compensate for much of the brains extra energy demand.
Aiello and Wheeler christened their idea the expensive tissue hypothesis. To test it, they compared the size
of brains and guts in a range of primate species (pdf). They found that the bigger a primates brain relative to
the speciess overall body size, the smaller the guts tend to be. This consistent trade-off suggested that
trimming our guts was essential to supersizing our brains.
Then William Leonard, a biological anthropologist at Northwestern University, put the expensive tissue
hypothesis to a new test. Instead of correlating brain and gut size across primate species, Leonard decided to
look at mammal species overall. Beyond the primates, he found, there existed no correlation whatsoever
between brain size and gut size.
This suggested that the gut-shrinking phenomenon within the primate groups was probably too subtle to
explain our increase in brain size completely. Something else had to be going on as well. That something,
Leonard says, is diet. After studying the diets of primate species and tallying the quantity and quality of food
consumed, Leonard found a switch from lower-energy diets of bark and leaves to higher-energy cuisines of
seeds, tubers, and meat in the brainier species. As brain-to-body ratio increases, presumably, the denser
calories supply the additional needed fuel.
Greg Wray, an evolutionary biologist at Duke University, is finding secrets to big brains in an entirely
different place: the human genome. One of the genes involved in feeding the big brain, called SLC2A1, builds
a protein for transporting glucose from blood vessels into cells. It is vital to the brains well-being. Mutations
that reduce the number of transporter proteins in the brain lead to disorders such as epilepsy and learning
disabilities. If one copy of the SLC2A1 gene is completely dysfunctional, the results are devastating: The

brain develops to only a portion of its normal size. If neither copy of the gene works, a fetus simply dies.
Wray and his colleagues compared SLC2A1 in humans and other animals. They discovered that our
ancestors acquired an unusually high number of mutations in the gene. The best explanation for that
accumulation of mutations is that SLC2A1 experienced natural selection in our own lineage, and the new
mutations boosted our reproductive success. Intriguingly, the Duke team discovered that the mutations
didnt alter the shape of the glucose transporters. Rather, they changed stretches of DNA that toggled the
SLC2A1 gene on and off.
Wray guessed that these mutations changed the total number of glucose transporters built in the human
brain. To test his theory, he looked at slices of human brain tissue. In order to make glucose transporters, the
cells must first make copies of the SLC2A1 gene to serve as a template. Wray discovered that in human
brains there were 2.5 to 3 times as many copies of SLC2A1 as there were in chimpanzee brains, suggesting
the presence of more glucose transporters as well.
Then he looked at glucose transporters that deliver the sugar to muscles. The gene for these muscle
transporters, called SLC2A4, also underwent natural selection in humans, but in the opposite direction. Our
muscles contain fewer glucose transporters than in chimps muscles. Wrays results support the notion that
our ancestors evolved extra molecular pumps to funnel sugar into the brain, while starving muscles by giving
them fewer transporters.
Becoming Homo megalencephalus was hardly a simple process. It was not enough for evolution to shrink
our gut and shift our diet. It had to do some genetic engineering, too.

Carl Zimmer is an award-winning biology writer and author of The Tangled Bank: An Introduction to
Evolution, among other books. His blog, The Loom, runs at blogs.discovermagazine.com/loom